The broad, long-term objective of the proposed research is development of a diagnostic imaging modality based on the polarization and coherent properties of light for anatomical and functional imaging of the eye. The underlying hypothesis for the proposed research is that in glaucomatous eyes optical birefringence of the retinal nerve fiber layer (NFL) displays a characteristic decrease with development and progression of the disease. Polarization-sensitive and depth-resolved measurement of light reflected from the retina can be used to determine both NFL thickness and axon density with unprecedented sensitivity and spatial resolution. Successful completion of the proposed research is expected to result in the development of a Polarization Sensitive Retinal Tomography (PSRT) methodology that will provide ophthalmologists a valuable imaging modality for detection and diagnosis of glaucoma. The specific aims of this proposal are to: 1) Design and construct a PSRT instrument utilizing active pixel photodetector arrays that provides high accuracy quantitative tomographic imaging measurements of the eye at video frame rates; 2) Using in vivo animal model studies, verify operation of the PSRT instrument to measure accurately the retinal nerve fiber layer (NFL) thickness and axon density; and 3) Conduct a clinical study to demonstrate how a diagnostic PSRT measurement offers a direct means of documenting retinal NFL thickness and axon density, and more importantly, provides the clinician a valuable imaging modality for the detection and diagnosis of glaucoma. Development of the PSRT instrument will be guided by studies proposed at three levels: 1) in-vivo and post-mortem studies using the New Zealand rabbit animal model to verify accuracy of PSRT measurements of NFL thickness and axon density; 2) characterization of the NFL atrophy in a primate model with induced glaucoma; and 3) clinical trials involving normal subjects and glaucoma patients to verify operation of the PSRT instrument to detect and diagnose glaucoma.